Potassium Channels in the Peripheral Microcirculation

Abstract

Vascular smooth muscle (VSM) cells, endothelial cells (EC), and pericytes that form the walls of vessels in the microcirculation express a diverse array of ion channels that play an important role in the function of these cells and the microcirculation in both health and disease. This brief review focuses on the K+ channels expressed in smooth muscle and endothelial cells in arterioles. Microvascular VSM cells express at least four different classes of K+ channels, including inward‐rectifier K+ channels (K IR), ATP‐sensitive K+ channels (K ATP), voltage‐gated K+ channels (K V), and large conductance Ca 2 +‐activated K+ channels (BK Ca). VSM K IR participate in dilation induced by elevated extracellular K+ and may also be activated by C‐type natriuretic peptide, a putative endothelium‐derived hyperpolarizing factor (EDHF). Vasodilators acting through cAMP or cGMP signaling pathways in VSM may open K ATP, K V, and BK Ca, causing membrane hyperpolarization and vasodilation. VSM BK Ca may also be activated by epoxides of arachidonic acid (EETs) identified as EDHF in some systems. Conversely, vasoconstrictors may close K ATP, K V, and BK Ca through protein kinase C, Rho‐kinase, or c‐Src pathways and contribute to VSM depolarization and vasoconstriction. At the same time K V and BK Ca act in a negative feedback manner to limit depolarization and prevent vasospasm. Microvascular EC express at least 5 classes of K+ channels, including small (sK Ca) and intermediate (IK Ca) conductance Ca 2 +‐activated K+ channels, K IR, K ATP, and K V. Both sK and IK are opened by endothelium‐dependent vasodilators that increase EC intracellular Ca 2 + to cause membrane hyperpolarization that may be conducted through myoendothelial gap junctions to hyperpolarize and relax arteriolar VSM. K IR may serve to amplify sK Ca‐ and IK Ca‐induced hyperpolarization and allow active transmission of hyperpolarization along EC through gap junctions. EC K IR channels may also be opened by elevated extracellular K+ and participate in K+‐induced vasodilation. EC K ATP channels may be activated by vasodilators as in VSM. K V channels may provide a negative feedback mechanism to limit depolarization in some endothelial cells.